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Biomedical subjects

W Lorenz

Publications and source records attributed to W Lorenz.

At least 19 recordsLinked to original sources
PubMed1995

Intravenous morphine and nalbuphine increase histamine and catecholamine release without accompanying hemodynamic changes.

Patients receiving intravenous morphine at doses of 0.3 and 1.0 mg/kg for general anesthesia have been reported to show significant elevations in plasma histamine that are associated with hemodynamic changes. We undertook a prospective, randomized, double-blind trial in which 0.15 mg/kg morphine or 0.3 mg/kg nalbuphine was administered intravenously to normal volunteers. Thirteen of 15 subjects receiving morphine and 10 of 14 subjects receiving nalbuphine had elevations in plasma histamine levels and symptoms of histamine release within 5 minutes of drug administration. Six subjects in the morphine group and five in the nalbuphine group exhibited levels of plasma histamine > 2.0 ng/ml, but these levels were not associated with hemodynamic changes and occurred 10 to 15 minutes after drug administration. Our study suggests that the opiate-induced elevation of plasma histamine derives from cutaneous mast cells.

Adolescent↗
PubMed1994

The role of high-dose, single-fraction irradiation in small and large intracranial arteriovenous malformations.

PURPOSE: Radiosurgery with external beam irradiation is an accepted treatment for small intracranial vascular malformations. It has been proven effective and safe for lesions with volumes of less than 4 cc. However, there is only some limited clinical data for malformations of grade 4 and grade 5, according to Spetzler and Martin. METHODS AND MATERIALS: At the Heidelberg radiosurgery facility equipped with a linear accelerator, 212 patients with cerebral arteriovenous malformations have been treated since 1984. Thirty-eight percent of the arteriovenous malformations treated were classified inoperable, 14% grade 5, 19% grade 4, and 29% grades 1-3. Radiation doses between 10 and 29 Gy were applied to the 80% isodose contour. RESULTS: Above a threshold dose of 18 Gy, the overall obliteration rate was 72%. After 3 years, the obliteration rates were 83% with volumes of less than 4.2 cc, 75% with volumes of up to 33.5 cc, and 50% with volumes of up to 113 cc. Of the patients presenting with seizures and paresis, 83% and 56%, respectively, showed improvement, which correlated with the degree of obliteration. After a follow-up period of up to 9 years, the rate of radiation-induced severe late complications was 4.3%. In grade 5 lesions, the risk of side effects was 10%. No serious complications occurred if a maximum dose of less than 25 Gy was applied to treatment volumes of less than 33.5 cc. CONCLUSION: The success of stereotactic high-dose irradiation of arteriovenous malformations depends on the dose applied. The incidence of radiation-induced side effects increased with the applied dose and treatment volumes. From our experience, doses of less than 25 Gy and treatment volumes of up to 33.5 cc are safe and effective. In the future, new techniques of radiosurgery with linear accelerators and dynamically reshaped beams will allow us to apply homogenous dose distributions. Additional use of magnetic resonance angiography for 3D treatment planning will help to identify the nidus more easily.

Adolescent↗
PubMed1994

Incidence and clinical importance of perioperative histamine release: randomised study of volume loading and antihistamines after induction of anaesthesia. Trial Group Mainz/Marburg.

Although histamine release is recognised as a common event during anaesthesia and surgery, few clinicians judge the resultant cardiorespiratory disturbances serious enough to warrant prophylaxis with antihistamines. We have assessed the incidence and importance of histamine release in a randomised 2 x 2 factorial study. 240 patients representing a routine throughput of major general surgery were studied during a standardised induction of anaesthesia and preoperative loading of the circulation with either Ringer solution or Haemaccel-35, with or without antihistamine prophylaxis with dimetindene (H1) plus cimetidine (H2). Cardiorespiratory disturbances were graded as detectable, clinically relevant, or life-threatening from observers' records of the anaesthesia and the actions taken by the anaesthetists. Disturbances that were accompanied by significant rises in plasma histamine were further designated histamine-related, and those that were not were designated histamine-unrelated. Anaesthetists, observers, and designators were blinded to whether or not the patients had received antihistamines and to which solution was used for circulatory volume loading. Clinically relevant or life-threatening histamine-related disturbances occurred in 8% of the patients who after induction of anaesthesia received Ringer without antihistamines, in 26% of those who received Haemaccel without antihistamines, and in 2% or less of those who received antihistamines (p < or = 0.0001). There were 4 life-threatening histamine-related disturbances, all in patients who received Haemaccel without antihistamines (p < 0.01). Histamine-unrelated disturbances occurred in 16% overall, with no obvious effect of Haemaccel or antihistamines. The histamine-related disturbances under anaesthesia were remarkable for their severity (even with small rises in histamine concentrations), for the prevalence of bradycardia, and for the absence of skin signs. Their likelihood and severity were increased in patients with tumours. The results of the trial make a case for routine prophylaxis with antihistamines as part of anaesthetic management.

Adolescent↗
PubMed1994

Unknown effects of clinically used drugs as bias in clinical trials: antihistaminergic activity of the antihypertensive fixed-dose combination Betathiazid.

In a controlled clinical trial on histamine release in anaesthesia, it was suspected that the antihypertensive fixed-dose combination drug Betathiazid masked clinical signs of histamine release. By structure analysis of its constituents (propranolol, triamterene and hydrochlorothiazide), hydrochlorothiazide was considered to be most likely an H1-antagonist. An aqueous solution of the whole drug tablet (2 x 10(-4) M propranolol, 2.9 x 10(-5) M triamterene, 1.7 x 10(-5) M hydrochlorothiazide) and of the individual substances (1 microM each) was tested in the classical H1-receptor assay using the guinea pig ileum. Betathiazid in total suppressed the contraction to histamine (78% inhibition), but not to carbachol. Propranolol and triamterene had depressive effects (14% and 38% inhibition), but hydrochlorothiazide potentiated the contractions to histamine (75% potentiation). In all cases, the type of antagonism was not competitive. Although different mechanisms may account for the modulatory effects of Betathiazid, they have to be considered in the interpretation of clinical studies, especially for relating mediator concentrations with clinical signs.

Animals↗
PubMed1994

Different collimators in convergent beam irradiation of irregularly shaped intracranial target volumes.

We compare different collimator forms (circular, elliptic and multi-leaf) in 3-D multiple arc rotation therapy for irregularly shaped intracranial tumors. When homogeneous irradiation of the tumor is ensured, the efficiency of treatment is expressed by the sparing of normal tissue outside the target volume to high dose irradiation. By utilizing integral dose-volume histograms we demonstrate that the multi-leaf collimator has considerable advantages.

Brain Neoplasms↗
PubMed1994

Time sequence of histamine release and formation in rat endotoxic shock.

Increased histamine release and formation (induced histamine) are two hypotheses considered in the pathogenesis of endotoxic shock development. To prove both hypotheses a sequence of four randomized controlled studies in rats was performed. Histamine release was measured indirectly as a decrease in tissue-histamine contents (lung, liver, spleen, stomach); histamine formation was estimated directly as an increase in histidine decarboxylase (HDC) activity in the same organs. Changes in contents and enzymatic activities were determined 4 and 8 h after shock induction; in addition, at the time of death, the activity of HDC was measured in heart, kidney, and small intestine. 4 h after shock induction, there was a significant decrease in the tissue-histamine content as measured only in the liver, with the same trend in lung and spleen. 8 h after endotoxin application, however, histamine concentration increased in the liver (significantly p < .05) and lung compared to the NaCl control group. The manifestation of changes in HDC activity in various organs was selective (i.e., not all organs showed alterations), not uniform (decreased as well as increased activities were measured), and time-dependent (no increase in HDC activity in animals dying at > 20 h). At 4 and 8 h, only the liver showed a strong increase in HDC activity which can explain the increase in histamine content. In lung, spleen, and stomach, a significant decrease occurred. The results on histamine release and formation let us conclude that histamine is involved in the pathogenesis of endotoxic shock development.

Animals↗
PubMed1994

Are hypotension and rash after atracurium really caused by histamine release?

A prospective, randomized, double-blind study was performed in 40 patients (ASA class I-III) treated with atracurium to ascertain whether histamine release caused hemodynamic or cutaneous changes. The treated group of 20 patients was premedicated with the H1 antagonist dimetindene (0.2 mg/kg) and the H2 antagonist ranitidine (1.25 mg/kg); the control group of 20 patients received saline. Six minutes after the induction of anesthesia with thiopental/fentanyl, patients received atracurium 0.5 mg/kg over 5 s. Plasma histamine levels were measured fluorometrically 5 min after administration of thiopental/fentanyl and 2 and 5 min after atracurium. Arterial blood pressure and heart rate were recorded every 2 min. Histamine levels (0.24 ng/mL) did not change significantly after thiopental/fentanyl. In the control group, 2 min after injection of atracurium, plasma histamine levels were 0.76 +/- 0.76 ng/mL, and in the antihistamine-treated group, 0.39 +/- 0.24 ng/mL (P < 0.05 control versus treated), suggesting that pretreatment with antihistamines may attenuate atracurium-induced histamine release. Systolic and diastolic blood pressure decreased significantly in both groups after thiopental (P < 0.05), but did not decrease further after the administration of atracurium. There were cutaneous manifestations in 7 of 20 patients in the control group and in none of the 20 patients treated with H1 and H2 antagonists (P < 0.0005). We conclude that atracurium caused modest histamine release in our patients but that the decrease in arterial blood pressure may have been due, in part, to thiopental. Cutaneous manifestations of histamine release did not correlate with hemodynamic events or with plasma histamine levels, but were prevented with antihistamine pretreatment.

Adolescent↗
PubMed1994

Granulocyte colony-stimulating factor prophylaxis before operation protects against lethal consequences of postoperative peritonitis.

BACKGROUND: Postoperative peritonitis has a high mortality in human beings. It is accepted that cytokines are important mediators in pathophysiology of sepsis. The recent failure of clinical trials increased the necessity to proof new drugs in more clinically relevant animal models. The aim of this study was to examine the effect of granulocyte colony-stimulating factor (G-CSF) in addition to an antibiotic in postoperative peritonitis. METHODS: Dose-response curves and experimental conditions were developed in a total of 295 rats. The main experiment included three groups: control animals receiving a fecal inoculum, a group treated with antibiotic, and a third group receiving G-CSF in addition to the antibiotic. The main outcome was death, but in addition, serum tumor necrosis factor (TNF) level was determined. RESULTS: The mortality rate of 60% in antibiotic treated animals was considerably reduced by G-CSF to 20%. All animals of the control group died during the observation period of 120 hours. A correlation between TNF levels and mortality rate was observed. In G-CSF treated animals total suppression of TNF serum levels was accessible in contrast to the others. CONCLUSIONS: In a clinically relevant animal model G-CSF was effective as an additional concept of prophylaxis. These data are promising toward clinical trials.

Animals↗
PubMed1994

[Measuring quality of life in after-care of tumor surgery. Methods, problems and applications].

The present paper deals with the feasibility and applications of quality of life measurement in the routine of a tumor follow-up clinic. 61 patients filled out the EORTC-30 questionnaire plus additional scales. Filling out the questionnaire constituted no burden for patients. Patients' responses were computed in a way as to allow for graphically presenting individual QL-profiles, as well as to compare different groups of patients. Considerations concerning the role of QL-measurement in clinical practice, in medical decision making, and in future research endeavours were brought forward.

Adaptation, Psychological↗
PubMed1993

Perioperative nonspecific histamine release: a new classification by aetiological mechanisms and evaluation of their clinical relevance.

As a consequence of the performance of a randomized controlled clinical trial on perioperative histamine release and cardiovascular and respiratory disturbances, several types of increases in plasma histamine had to be distinguished instead of only two which existed at the beginning of the study: drug-induced allergic and pseudoallergic reactions. First of all, the new classification by aetiology (clinical epidemiology) was derived from a meta-analysis (secondary analysis) of the most recent literature. According to that histamine release in the perioperative period has several, different causes and is involved in several, different disease manifestations. A clear distinction (classification), however, is necessary if histamine release as an unwanted (adverse) effect has to be recognized, value judged according to its clinical relevance and therefore also prevented by histamine antagonists. Histamine release by neuro-endocrine and neuro-inflammatory mechanisms, cytotoxic histamine release and local, cytokine induced histamine release have been distinguished from pseudoallergic histamine release, but its functions are not yet clear. It has been analysed in prospective trials which used special clinical situations as models: patients on a normal ward or before and during upper GI endoscopy without premedication, but also in specific phases of laparoscopic cholecystectomy (trocar phase and dissection phase). Their existence in the clinical reality is now very likely, but new trials must investigate the pathophysiological effects such as in metabolism, coagulation, pulmonary haemodynamics (shunt volume) and gastric acid secretion. Histamine release by pseudoallergic mechanisms, however, was identified in the very vulnerable post-induction phase of anaesthesia up to skin incision. Its incidence was much higher than ever expected and its clinical relevance was demonstrated by the severity of reactions and the intervention strategies of the anaesthetists who were blinded concerning the type of the plasma substitute given and the prophylaxis with antihistamines. Pseudoallergic histamine release was clearly unwanted (adverse). Its occurrence in the other phases of anaesthesia has to be further evaluated in the tedious procedure of data analysis of the Mainz-Marburg-trial. The overall incidence of histamine release in the trial was so incredible high (72% of all patients, some of them with up to 4 episodes of histamine release) that a distinction between pseudoallergic (unwanted) and other types of histamine release (possibly less unwanted or even beneficial) is urgently needed. In the phase of steady state (maintenance) of anaesthesia the H1-(+)H2-prophylaxis was highly effective. Further analysis must show whether this is also the case during the phases of induction of anesthesia.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Histamine release after injection of benzodiazepines and of etomidate. A problem associated with the solvent propylene glycol.

Many drugs, especially when given in rapid sequence can cause histamine release. Ten healthy volunteers were premedicated with diazepam 10 mg.70 kg-1 i.v. and lormetazepam 1 mg.70 kg-1 i.v., respectively, 30 min prior to etomidate 0.15 mg.kg-1 i.v. in a single-blind, crossover study. The benzodiazepine lormetazepam and the hypnotic etomidate caused distinct increases in histamine plasma levels in two subjects. Maximal histamine levels after lormetazepam were 2.05 and 2.7 ng.ml-1, and after etomidate 1.85 and 3.2 ng.ml-1, respectively. Both drugs are solved in propylene glycol, a solvent that conveys very high osmolality (lormetazepam 6,750 mosm.kg-1, etomidate 4,900 mosm.kg-1). Clinical symptoms, like tachycardia, hypotension or allergic reactions, associated with similar histamine levels were not seen in either case. This limited histamine release appears to be caused by osmotic damage of tissue and blood cells.

Adult↗